Gross Tumor and Intracranial Control Benefits with Fractionated Radiotherapy Compared with Stereotactic Radiosurgery for Patients with WHO Grade 2 Meningioma.

OBJECTIVE: Surgical resection is the mainstay of treatment for WHO grade 2 meningioma. Fractionated radiation therapy (RT) is frequently used after surgery, though many centers utilize stereotactic radiosurgery (SRS) for recurrence or progression. Herein, we report disease control outcomes from an institutional cohort with adjuvant fractionated RT versus salvage SRS. METHODS: We identified 32 patients from an institutional database with WHO grade 2 meningioma and residual/recurrent tumor treated with either SRS or fractionated RT. Patients were treated between 2007 and 2021 and had at least 1 year of follow-up. Kaplan-Meier estimators were used to determine gross tumor control (GTC) and intracranial control (IC). Univariate Cox proportional hazards models using biologically effective dose (BED) as a continuous parameter were used to assess for dose responses. RESULTS: With a median follow-up of 5.5 years, 13 patients (41%) received SRS to a recurrent or progressive nodule, 2 (6%) fractionated RT to a recurrent or progressive nodule, and 17 (53%) adjuvant fractionated RT following subtotal resection. Five-year GTC was higher with fractionated RT versus SRS (82% vs. 38%, P = 0.03). Five-year IC was also better with fractionated RT versus SRS (82% vs. 11%, P < 0.001). On univariate analysis, increasing BED10 was significantly associated with better GTC (P = 0.039); increasing BED3 was not (P = 0.82). CONCLUSIONS: In this patient cohort, GTC and IC were significantly higher in patients treated with adjuvant fractionated RT compared with salvage SRS. Increasing BED10 was associated with better GTC. Fractionated RT may provide a better therapeutic ratio than SRS for grade 2 meningiomas.

Gene Expression Patterns Associated with Survival in Glioblastoma.

The aim of this study was to investigate gene expression alterations associated with overall survival (OS) in glioblastoma (GBM). Using the Nanostring nCounter platform, we identified four genes (COL1A2, IGFBP3, NGFR, and WIF1) that achieved statistical significance when comparing GBM with non-neoplastic brain tissue. The four genes were included in a multivariate Cox Proportional Hazard model, along with age, extent of resection, and O6-methylguanine-DNA methyltransferase (MGMT) promotor methylation, to create a unique glioblastoma prognostic index (GPI). The GPI score inversely correlated with survival: patient with a high GPI had a median OS of 7.5 months (18-month OS = 9.7%) whereas patients with a low GPI had a median OS of 20.1 months (18-month OS = 54.5%; log rank p-value = 0.004). The GPI score was then validated in 188 GBM patients from The Cancer Genome Atlas (TCGA) from a national data base; similarly, patients with a high GPI had a median OS of 10.5 months (18-month OS = 12.4%) versus 16.9 months (18-month OS = 41.5%) for low GPI (log rank p-value = 0.0003). We conclude that this novel mRNA-based prognostic index could be useful in classifying GBM patients into risk groups and refine prognosis estimates to better inform treatment decisions or stratification into clinical trials.

Differentiation of survival outcomes by anatomic involvement and histology with the revised 2023 International Federation of Gynecology and Obstetrics staging system for endometrial cancer.

OBJECTIVES: The International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer underwent revision in 2023, incorporating histology, lymphovascular space invasion, and molecular classification. Herein, we compare overall survival (OS) outcomes by anatomic and histologic involvement for patients staged by the 2009 system versus 2023 system. METHODS: The National Cancer Database (NCDB) was queried for patients with newly-diagnosed uterine adenocarcinoma from 2004 to 2015, with follow-up data extending through 2020. Stage was determined by both the 2009 and 2023 FIGO staging systems. Kaplan-Meier estimators and Cox proportional hazards models were used for survival analysis. RESULTS: A total of 134,677 patients were analyzed. Per 2023 classification, patients with stage I disease decreased from 96,161 to 70,101 (-27.1%, p < 0.01), while stage II disease increased from 9295 to 36,294 (+390.5%, p < 0.01). Greatest OS change was observed for 2023 stage IA3 patients (low-risk, synchronous endometrial and ovarian tumors with a clonal relationship), whose 10-year OS was 73.4%, compared to 52.6% for 2009 stage IIIA disease. Ten-year OS for 2023 stage IIIB2 (pelvic peritoneal involvement), previously 2009 stage IVB, was 49.4%, compared to 18.7% for 2009 stage IVB patients. Akaike information criterion, Bayesian information criterion, and Harrel's concordance index were used to evaluate OS prognostication of each staging system across all stages, with likelihood ratio favoring the 2023 system (p = 0.020). CONCLUSIONS: With FIGO's 2023 endometrial cancer anatomic and histologic staging system, stage migration is greatest in early-stage disease. New staging groups may offer more precise prognostication. These changes may affect future management.

Patterns of failure after radiosurgery for WHO grade 1 or imaging defined meningiomas: Long-term outcomes and implications for management.

BACKGROUND: We analyzed long-term control and patterns of failure in patients with World Health Organization Grade 1 meningiomas treated with definitive or postoperative stereotactic radiosurgery at the authors' affiliated institution. METHODS: 96 patients were treated between 2004 and 2019 with definitive (n = 57) or postoperative (n = 39) stereotactic radiosurgery. Of the postoperative patients, 17 were treated adjuvantly following subtotal resection and 22 were treated as salvage at time of progression. Patients were treated to the gross tumor alone without margin or coverage of the dural tail to a median dose of 15 Gy. Median follow up was 7.4 years (inter-quartile range 4.8-11.3). Local control, marginal control, regional control, and progression-free survival were analyzed. RESULTS: Local control at 5 and 10 years was 97 % and 95 %. PFS at 5 and 10 years was 94 % and 90 % with no failures reported after 6 years. Definitive and postoperative local control were similar at 5 (95 % [82-99 %] vs. 100 %) and 10 years (92 % [82-99 %] vs. 100 %). Patients treated with postoperative SRS did not have an increased marginal failure rate (p = 0.83) and only 2/39 (5 %) experienced recurrence elsewhere in the cavity. CONCLUSIONS: Stereotactic radiosurgery targeting the gross tumor alone provides excellent local control and progression free survival in patients treated definitively and postoperatively. As in the definitive setting, patients treated postoperatively can be treated to gross tumor alone without need for additional margin or dural tail coverage.

National trends in endovascular thrombectomy and decompressive craniectomy for acute ischemic stroke: A study using National Inpatient Sample data from 2006 to 2016.

BACKGROUND: Ischemic stroke is a frequently encountered neurologic process with wide-spanning impact. A dreaded complication is "malignant" cerebral edema, necessitating decompression to reduce herniation risk. Following the publication of several landmark trials in 2015, endovascular thrombectomy (EVT) with novel clot-removal devices has emerged as an effective treatment for proximal large vessel disease. Herein, we examine recent national trends in EVT and decompressive craniectomy (DC) rates for acute stroke. METHODS: National Inpatient Sample data were abstracted from 2006 to 2016. Primary outcomes were EVT and DC rates, compared using Cochrane-Armitage test of trend. Chi-square test was also used to compare data from 2015 to 2016. Secondary outcomes included inpatient mortality and home discharge rates. RESULTS: EVT rates steadily increased from 2006 to 2016, with most change occurring from 2014 to 2016 (1.36% in 2014, 2.29% in 2016). DC rates similarly increased from 2006 to 2015, though a sharp decline was observed in 2016 (0.42% in 2015, 0.22% in 2016). Test of trend from 2006 to 2016 for both variables was found to be statistically significant (p = 0.001); DC rate change from 2015 to 2016 was also statistically significant (p < 0.01). Mortality rate and home discharge rate steadily improved over the study period. CONCLUSIONS: Recent innovation in stroke treatment has led to increased EVTs. While DC rate initially followed this same trend, a significant decline was noted in 2016, around the time that wider adoption of novel EVT technologies were instituted in clinical practice.

Asleep Deep Brain Stimulation of the Nucleus Ventralis Intermedius for Essential Tremor Using Indirect Targeting and Interventional Magnetic Resonance Imaging: Single-Institution Case Series.

BACKGROUND: Literature on asleep deep brain stimulation (DBS) of the ventralis intermedius (Vim) nucleus in essential tremor is relatively sparse. Furthermore, controversy exists as to whether indirect ("consensus" or "atlas-based") targeting of the Vim requires physiologic adjustment for effective clinical outcomes in DBS surgery. OBJECTIVES: The objective of this study was to evaluate the clinical results of asleep Vim DBS using indirect coordinates and real-time interventional magnetic resonance imaging guidance. METHODS: Retrospective review of a prospectively collected database was performed to identify patients with essential tremor undergoing asleep Vim DBS using interventional magnetic resonance imaging guidance. Stereotactic and clinical outcomes were abstracted and analyzed using descriptive statistics. RESULTS: A total of 12 consecutive patients were identified, all of whom were available for 6-month clinical follow-up. Stereotactic (radial) error was 0.5 ± 0.2 mm on the left and 0.5 ± 0.3 mm on the right. Fahn-Tolosa-Marin tremor scores in the treated limb(s) decreased by 71.2% ± 31.0% (P = 0.0088), The Essential Tremor Rating Assessment Scale activities of daily living improved by 74.9% ± 23.7% (P < 0.0001), and The Essential Tremor Rating Assessment Scale performance improved by 64.3 ± 16.2% (P = 0.0004). Surgical complications were mild and generally transient. Stimulation-related side effects were similar to those reported in historical series of awake Vim DBS. CONCLUSIONS: Asleep Vim DBS using indirect targeting and interventional magnetic resonance imaging-guided placement is safe and effective, with 6-month clinical results similar to those achieved with awake placement. These data support the use of asleep surgery in essential tremor and represent a baseline for comparison with future studies using more advanced targeting techniques.

Resumption of Positive-Pressure Ventilation Devices for Obstructive Sleep Apnea following Transsphenoidal Surgery: An Institutional Experience of a Surgical Cohort.

Objectives Transsphenoidal surgery creates a skull base defect that may cause postoperative cerebrospinal fluid (CSF) leakage or pneumocephalus. This study reviewed the institutional experience of a pituitary center in managing patients who use positive-pressure ventilation (PPV) devices for obstructive sleep apnea (OSA) after transsphenoidal surgery, which risks disturbing the skull base repair. Design Retrospective review. Setting Pituitary referral center in a major metropolitan medical center. Methods PPV was resumed at the discretion of the treatment team based on intraoperative findings and OSA severity. Perioperative complications related to resuming and withholding PPV were recorded. Participants Transsphenoidal surgery patients with OSA using PPV devices. Main Outcome Measures Intracranial complications before and after resuming PPV. Results A total of 42 patients met the study criteria. Intraoperative CSF leakage was encountered and repaired in 20 (48%) patients. Overall, 38 patients resumed PPV (median: 3.5 weeks postsurgery; range: 0.14-52 weeks) and 4 patients did not resume PPV. Postoperatively, no patient experienced CSF leakage or pneumocephalus before or after resuming PPV. Four (10%) patients required temporary nocturnal supplemental oxygen at home, one patient was reintubated after a myocardial infarction, and one patient had a prolonged hospital stay due to chronic obstructive pulmonary disease exacerbation. Conclusions Resuming PPV use after transsphenoidal surgery did not result in intracranial complications. However, delay in resuming PPV resulted in four patients requiring oxygen at home. We propose a preliminary PPV device management algorithm based on the size of the intraoperative CSF leak to facilitate future studies.

Advanced Imaging and Direct Targeting of the Motor Thalamus and Dentato-Rubro-Thalamic Tract for Tremor: A Systematic Review.

Direct targeting methods for stereotactic neurosurgery in the treatment of essential tremor have been the subject of active research over the past decade but have not yet been systematically reviewed. We present a clinically oriented topic review based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses Group guidelines. Our focus is studies using advanced magnetic resonance imaging (MRI) techniques (ultrahigh-field structural MRI, diffusion-weighted imaging, diffusion-tensor tractography, and functional MRI) for patient specific, in vivo identification of the ventral intermediate nucleus and the dentato-rubro-thalamic tract.

Deep Brain Stimulation Surgery for Essential Tremor in a Patient with Type A Hemophilia.

BACKGROUND: Hemophilia is generally considered a contraindication to deep brain stimulation (DBS) and other elective intracranial surgery because of the elevated risk of perioperative hemorrhage. Two prior case reports have suggested, however, that DBS may be safe in patients with hemophilia who undergo appropriate factor replacement. Here, we describe a third case of DBS surgery for medically refractory essential tremor (ET) in a patient with hemophilia A. CASE DESCRIPTION: A 68-year-old right-handed man with mild hemophilia A presented for a 10-year history of bilateral (right greater than left), medically refractory ET. The patient was considered an appropriate candidate for DBS by a multidisciplinary movement disorders conference, and hematology consultation was obtained. Baseline preoperative laboratory results showed a quantitative factor VIII (FVIII) level of 38%. Perioperative management consisted of daily intravenous bolus doses of recombinant FVIII from the morning of surgery to postoperative day 10. The patient underwent uncomplicated unilateral DBS placement in the left ventralis intermedius thalamus. Intra- and postoperative imaging showed no hemorrhage. His postoperative course was uncomplicated except for a single self-limited episode of hematuria requiring no intervention. CONCLUSIONS: DBS placement for ET may be safe in patients with coexisting hemophilia A if appropriate FVIII replacement is given, which may be delivered as bolus infusions rather than continuous infusion.

Laparoscopically Assisted Ventriculoperitoneal Shunt Placement Is not Cost-Effective nor Preventive for Distal Shunt Malfunction.

BACKGROUND: Laparoscopy for ventriculoperitoneal shunt creation might offer smaller incisions and more reliable placement. We assessed the reliability and cost-effectiveness of this technique compared with mini-laparotomy shunt placement. METHODS: All patients undergoing ventriculoperitoneal shunt creation between November 2013 and September 2017 at a single academic institution were evaluated. Individual cases were assessed for the use of laparoscopy for peritoneal shunt placement (laparoscopy) versus mini-laparotomy for peritoneal shunt placement (open). The direct hospital costs for the laparoscopy and open groups were compared for elective shunt placement from the Vizient database. These direct costs were the proportion of the admission cost attributed to surgery. The primary endpoints included costs and revision of the peritoneal catheter within 12 months of the index procedure. RESULTS: A total of 68 patients met the inclusion criteria. Most cases (n = 40; 58.8%) had been performed with laparoscopy, with 28 performed using an open peritoneal approach. Three patients had required ≥1 distal shunt revision: 2 laparoscopy patients (5.0%; 1 had required a second revision) and 1 open patient (3.6%). No statistically significant differences were found for the patients requiring distal shunt revision between the 2 groups (P = 1.000; Fisher's exact test). The direct cost ($9461) of ventriculoperitoneal shunt creation with laparoscopy was greater than that with an open approach ($8247; P = 0.033). CONCLUSIONS: Both laparoscopy and open peritoneal shunt creation are safe procedures, with a 12-month distal revision rate in the present series of ~4%. Laparoscopy provided no relative improvement in safety or complication avoidance but had resulted in a mean increase in costs of >$1200 per patient.

Safe Transition to Pembrolizumab following Ipilimumab-Induced Guillain-Barré Syndrome: A Case Report and Review of the Literature.

BACKGROUND: Immune checkpoint inhibitors are novel therapies with indications for treating several solid cancers. They are associated with immune-related adverse events, which are generally well tolerated. Though rare, severe side effects may be life-threatening. One such adverse event is Guillain-Barré syndrome, which requires cessation of the immunotherapy and intravenous immunoglobulin and/or high-dose steroids to treat. No recommendations have been published regarding restarting cancer treatment after development of immunotherapy-induced Guillain-Barré syndrome. CASE PRESENTATION: A 71-year-old gentleman with recurrent, stage IIIB melanoma was started on ipilimumab (cytotoxic T lymphocyte antigen-4 inhibitor) for adjuvant treatment following radical neck dissection and radiation therapy. After completing his third cycle of ipilimumab, he developed rapidly progressive ascending paralysis. He was diagnosed with ipilimumab-induced atypical Guillain-Barré syndrome and was treated with intravenous immunoglobulin and corticosteroids. Ipilimumab was discontinued, and the patient was monitored via surveillance imaging, as there was no evidence of active disease at that time. Several months later, he was found to have recurrent disease involving the lung, requiring right lower lobectomy. Restaging revealed thoracic lymph node involvement, and he was then started on pembrolizumab (programmed cell death protein-1 inhibitor). He experienced a complete tumoral response to pembrolizumab, and he tolerated treatment well without recurrent weakness. CONCLUSIONS: Guillain-Barré syndrome is a rare but severe complication associated with immunotherapy. Our findings suggest that in patients with a history of ipilimumab-induced Guillain-Barré syndrome, pembrolizumab may possibly be a safe and effective alternative for cancer therapy.

Severe Drug-Induced Liver Injury from Combination Encorafenib/Binimetinib.

Encorafenib/binimetinib is a new combination BRAF/MEK inhibitor used in the treatment of advanced or metastatic BRAFV600-mutant melanoma. Though generally tolerated well, mild to moderate aminotransferase elevations are common. However, significant liver injury has not been demonstrated in the literature. Here, we report the first case of severe hepatic injury associated with encorafenib/binimetinib in a 58-year-old gentleman requiring admission and extensive workup. He was successfully treated by withdrawing the combination therapy, and liver function returned to normal range.

Therapeutic Monoclonal Antibodies Targeting Immune Checkpoints for the Treatment of Solid Tumors.

Recently, modulation of immune checkpoints has risen to prominence as a means to treat a number of solid malignancies, given the durable response seen in many patients and improved side effect profile compared to conventional chemotherapeutic agents. Several classes of immune checkpoint modulators have been developed. Here, we review current monoclonal antibodies directed against immune checkpoints that are employed in practice today. We discuss the history, mechanism, indications, and clinical data for each class of therapies. Furthermore, we review the challenges to durable tumor responses that are seen in some patients and discuss possible interventions to circumvent these barriers.

Multiple Extraaxial Cavernous Hemangiomas: Rare Entity.

BACKGROUND: Cavernous hemangiomas arising in the extraaxial space are rarely encountered, often mimicking other more common pathologies. Furthermore, multiple coexisting lesions and posterior fossa involvement are scarcely reported. Herein, we present the case of a patient with concurrent frontal bone and posterior fossa extraaxial cavernous hemangiomas. We also review the challenges associated with the diagnosis and management of these entities. CASE DESCRIPTION: An otherwise healthy 41-year-old gentleman presented with a 7-month history of a progressive right forehead mass. Imaging demonstrated a right frontal bone mass and an incidentally noted transverse sinus-based mass. The patient opted for surgical resection of both lesions. A right frontal craniotomy was performed to remove the bony lesion, followed by a suboccipital approach for the dural-based mass. There were no significant complications intraoperatively, and gross total resection was achieved for both lesions. Final pathology for each was consistent with cavernous hemangioma. CONCLUSIONS: Extraaxial cavernous hemangiomas are uncommon clinical entities that are challenging to distinguish from other diseases. If intraoperative complications can be avoided, treatment with surgical resection often offers excellent patient outcomes.

The Minimal Clinically Important Difference of the Anterior Skull Base Nasal Inventory-12.

BACKGROUND: The minimal clinically important difference (MCID) is defined as the smallest change in health-related quality of life (QOL) that patients consider meaningful. The MCID is essential for determining clinically significant changes, rather than simply statistically significant changes, in QOL scores. The Anterior Skull Base Nasal Inventory-12 (ASK Nasal-12), a site-specific sinonasal QOL instrument, has emerged as a standard instrument for assessing QOL in patients who have undergone endonasal transsphenoidal surgery. OBJECTIVE: To determine the MCID for the ASK Nasal-12. METHODS: Distribution- and anchor-based methods were used to determine the MCID for the ASK Nasal-12 based on raw data from a multicenter prospective QOL study of 218 patients. RESULTS: Two distribution-based statistical methods, the one-half standard deviation method and the effect-size method, both yielded MCIDs of 0.37 (medium effect). The first anchor-based method, using the 2-wk postoperative overall nasal functioning item as the anchor, yielded an MCID of 0.31. The second anchor-based method, using the 2-wk postoperative Short Form Health Survey 8 bodily pain item as the anchor, yielded an MCID of 0.29. CONCLUSION: The largest MCID obtained for the ASK Nasal-12 using 4 statistical methods 2 wk postoperatively was 0.37. This information provides clinicians with an essential context for determining the clinical significance of changes in QOL scores after interventions. Our results will help clinicians better interpret QOL scores and design future studies that are powered to detect meaningful QOL changes.